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Biomedical subjects

S Kaye

Publications and source records attributed to S Kaye.

At least 55 records · Page 3Linked to original sources
PubMed1988

Quantification of brainstem auditory evoked responses for patient monitoring.

A method of quantifying the integrity of the brain stem auditory evoked responses (BAERs) is applied to specific cases in both the ICU and OR to demonstrate its usefulness as an adjunct to peak latency evaluation. This measure is particularly valuable when peak identification is difficult as a result of poor waveform coherence. Examples are included to demonstrate that this method can also give independent information from peak latency.

Brain Stem↗
PubMed1988

Phase II study of iproplatin (CHIP, JM-9) in advanced testicular cancers progressing after prior chemotherapy.

Twenty-two patients with advanced testicular cancer received iproplatin at a dose of 180-240 mg/m2 every 4 weeks. All the patients progressed or recurred after chemotherapy including cisplatin. The most severe toxicity was thrombocytopenia with two toxic deaths after a first cycle of 240 and 180 mg/m2 respectively. Nausea and vomiting were almost universal but mild in intensity. One renal failure occurred 6 weeks after the first cycle while the tumor was progressing. No antitumor activity was observed in this heavily pretreated population of patients.

Adult↗
PubMed1988

Phase II study of iproplatin in advanced ovarian carcinoma.

Iproplatin (cis-dichloro-trans dihydroxy-bis-isopropyl-amine platinum [IV]; CHIP) was administered intravenously (IV) at monthly intervals at doses of 300 mg/m2 and 240 mg/m2 to ten previously untreated and 97 previously treated patients with advanced ovarian carcinoma. The overall response rate was 78% among patients with no prior chemotherapy, 42% among patients with prior chemotherapy not including cisplatin, and 22% among patients with prior chemotherapy including cisplatin. Overall response rates to iproplatin were 6.4% and 54% in patients with/without clinical evidence of tumor resistance to cisplatin. Thrombocytopenia was the dose-limiting toxicity, median time to nadir and to recovery being 2 and 4 weeks, respectively. Patients who had received prior chemotherapy regimens for greater than 1 year showed a 10% greater reduction in platelet count (mean platelet nadir +/- SD, 57.5 +/- 49.96 X 10(3)/microL) and a higher incidence of grade 3 to 4 thrombocytopenia after the first cycle than patients who had received prior chemotherapy regimens for less than 1 year (94.7 +/- 65.99 X 10(3)/microL) Moderate to severe vomiting and diarrhea occurred in 84% and 16% of patients pretreated with chemotherapy. Neuropathy (6%) was reported only in patients with prior cisplatin treatment. Mild and reversible renal toxicity was observed in 6% of cases. Iproplatin is an active drug in ovarian cancer; the results achieved in patients previously treated with cisplatin strongly suggest that the two drugs are cross-resistant.

Antineoplastic Agents↗
PubMed1987

Multicenter study of trilostane: a new hormonal agent in advanced postmenopausal breast cancer.

Trilostane, an inhibitor of the production of adrenal estrogens, was administered, together with dexamethasone, to 97 eligible postmenopausal women with advanced breast cancer. Seventy-four patients who had either received trilostane for a minimum of 10 weeks or whose disease had progressed while on trilostane before this period were assessed for tumour response. Eighteen patients (25%) had objective responses (two complete, 16 partial); a further 21 patients had stable disease. The response rate among all 97 patients, including those not treated for a minimum 10-week period, was 19%. Thirty-two of 97 patients reported adverse reactions which were attributed to trilostane and/or dexamethasone. Therapy was stopped for 15 patients, and the dose of trilostane was reduced for ten. Diarrhea was the commonest side effect, being reported in 16 patients, of whom nine stopped treatment. Trilostane, given with a corticosteroid, is an effective alternative hormonal agent acting by adrenal blockade for postmenopausal women with advanced breast cancer.

Breast Neoplasms↗
PubMed1986

Marked inter-patient variation in adriamycin biotransformation to 7-deoxyaglycones: evidence from metabolites identified in serum.

Several factors are known to modulate the clinical pharmacokinetics of adriamycin (ADR). Biotransformation has not been studied in this context because of problems identifying serum metabolites. We have studied patterns of ADR biotransformation in 25 patients with normal liver and kidney function and in most cases receiving ADR for the first time. Three major serum metabolites were identified by HPLC, TLC and mass spectrometry and their pharmacokinetics were followed over a 24-hr period. The relative amount of each metabolite present in a patient was quantitated by calculating its AUC. Adriamycinol was the major metabolite detected in the majority of patients. Adriamycin 7-deoxyaglycone was detected in the serum of 15 patients where it accounted for a small percentage of the total ADR concentration (1-5%). Its apparent half-life was normally less than 30 min. Adriamycinol 7-deoxyaglycone was detected in the serum of only 13 patients where it accounted for a greater percentage of the total ADR concentration (10-20%). Its pharmacokinetics exhibited marked inter-patient variations, with apparent half-lives ranging from 0.1 to 24 hr. There was a correlation between the AUC of ADR and the relative amount of metabolites present in each patient (r = 0.73). Thus, biotransformation may explain, partly, inter-patient variations in ADR pharmacokinetics. In turn, variations in biotransformation are dictated by whether or not ADR is converted to 7-deoxyaglycones.

Biotransformation↗
PubMed1985

A randomised trial of tamoxifen versus tamoxifen with aminoglutethimide in post-menopausal women with advanced breast cancer.

Sixty-six post-menopausal women with metastatic breast cancer were randomised to receive tamoxifen or tamoxifen with aminoglutethimide. The women in the tamoxifen group were virtually free of toxicity, whilst 45% of patients in the aminoglutethimide group had toxicity and 13% discontinued the drug because of this. Responses were seen in 19% of patients receiving tamoxifen alone and 23% of those receiving both drugs. There is no indication that the increased toxicity seen with the addition of aminoglutethimide to tamoxifen in this situation is justified by an increased response rate.

Aged↗
PubMed1985

Tumour cell resistance to anthracyclines--a review.

Resistance to anthracyclines is the major factor limiting their clinical utility. Laboratory studies using cultured experimental and human tumour cells have indicated that reduced intracellular drug accumulation is one important factor underlying resistance. In some systems this results from enhanced active drug efflux, a process which may be circumvented experimentally, for example by calcium antagonists. A specific glycoprotein which is produced in excess and is inherited has been identified in the cell membrane of certain anthracycline-resistant cells, while gene amplification with the appearance of double-minute chromosomes has been noted in others. Thus it is possible that anthracycline resistance arises following inherited changes in the cell membrane resulting in failure of drug accumulation. However, other possibilities exist, including differences in drug binding, either to the cell membrane or to nuclei, differences in metabolism to the semiquinone free radical, and differences in drug penetration related to tumour morphology. For each human tumour type the factor(s) involved may differ, but sufficient clues now exist to suggest that clinical testing of some of the therapeutic possibilities for circumventing anthracycline resistance may soon be appropriate.

Animals↗
PubMed1985

Malignant phaeochromocytoma.

Malignant phaeochromocytoma is a rare tumour and experience in its management is therefore limited. Five patients are discussed in whom the development of metastases was associated with rapidly progressive disease.

Adrenal Gland Neoplasms↗
PubMed1985

Response threshold determination of the brain stem auditory evoked response: a comparison of the phase versus magnitude derived from the fast Fourier transform.

An ensemble of 10 groups of brain stem evoked responses (BAERs), each consisting of 200 sweeps, was collected for different intensity levels and for a no-stimulus condition. A fast Fourier transform was calculated for the separate groups, which permitted a phase variance to be derived. The phase variance was compared to the magnitude value for selected frequency components making up the BAER. It was found that the phase variance was a better predictor of signal than magnitude. The superiority of prediction by phase results from intersubject variation being smaller for phase compared to magnitude.

Acoustic Stimulation↗
PubMed1985

The role of VP-16 in the treatment of small-cell lung cancer: studies of the West of Scotland Lung Cancer Group.

Reviews of published studies indicate that the incorporation of VP-16 (Vepesid) into combination chemotherapy for small-cell lung cancer may improve overall response rates from 50% to between 65% and 80%. In addition, high-dose VP-16 may yield a higher response rate than that obtained with conventional doses. The West of Scotland Lung Cancer Group has therefore conducted studies to examine the effects of VP-16 both in a combination regimen as induction therapy and (together with high-dose cyclophosphamide) as late intensification therapy in high dose, aimed at preventing relapse in responding patients. Response to induction treatment improved with the addition of VP-16, compared to earlier studies carried out by the group, yielding an overall response rate of 80% for patients with limited disease and 62% for those with extensive disease. Although induction therapy comprised only three courses (lasting 9 weeks), the median response duration of 9.5 months for complete responders and the median survival of 14 months for complete responders (limited disease) were in keeping with those obtained using more prolonged induction therapy. The intensification therapy with high-dose cyclophosphamide and high-dose VP-16, however, yielded no improvement in overall survival in those responding patients who received it compared with those who did not. Radiotherapy following late-dose intensification prevented local tumor recurrence but appeared to have no effect on overall survival. Resistance to VP-16 and other drugs is a possible deterrent to successful therapy in small-cell lung cancer, and it is suggested that research focus on a possible role for calcium channel blockers in circumventing drug resistance.

Carcinoma, Small Cell↗
PubMed1984

Treatment of advanced ovarian cancer with combination chemotherapy using cyclophosphamide, adriamycin and cis-platinum.

Fifty-four patients with advanced ovarian cancer have been treated with combination chemotherapy using cyclophosphamide, adriamycin and cis-platinum. The toxicity of the regimen was manageable but few patients were prepared to tolerate more than 6 months of treatment. Those in complete clinical remission at that time were offered second-look laparotomy and if apparently free of disease, therapy was discontinued. Forty-seven patients could be assessed of whom 33 had had no previous therapy. Twenty-two of these were clinically free of disease after completion of chemotherapy of whom 12 had no detectable disease at second-look laparotomy. Of 14 patients who had failed previous therapy only one remains clinically free of disease. The results in the untreated patients demonstrate the primary importance of bulk reduction at initial laparotomy. The use of the regimen in patients who have failed on previous treatment or in patients with bulk disease seems to be palliative and the toxicity should be assessed in this context.

Adult↗
PubMed1984

A quantitative assessment of the brain stem auditory evoked response during intraoperative monitoring.

The brain stem auditory evoked response (BAER) was monitored intraoperatively in 11 patients with tumors of the posterior fossa. A technique for the objective quantitative assessment of the BAER based on the variance of the phase angle between small group averages is described. The resulting component synchrony measure corroborated standard peak latency and amplitude changes of the BAER during operative manipulation. A discussion of the replication and use of the objective measure is presented.

Brain Stem↗
PubMed1983

Oral levonantradol in the control of cancer chemotherapy-induced emesis.

A dose-ranging study with oral levonantradol was performed in 20 cancer patients. The optimum oral dose which attenuated vomiting accompanying chemotherapy was 1 mg 4-hourly. Side-effects comprised dizziness, confusion, euphoria, drowsiness, and difficulty in concentrating. There was no cardiovascular toxicity. Overall toxicity appeared to be dose-related and was mild and acceptable.

Antiemetics↗
PubMed1983

A randomised multicentre single blind comparison of a cannabinoid anti-emetic (levonantradol) with chlorpromazine in patients receiving their first cytotoxic chemotherapy.

One hundred and eight patients selected to receive combinations of highly emetic cytotoxic chemotherapy for malignant disease were included in a study of anti-emetic therapy. The patients were randomly allocated to receive levonantradol (0.5, 0.75 or 1 mg) or chlorpromazine (25 mg) prior to receiving their first course of cytotoxic therapy. The appropriate anti-emetic was administered 2 hr prior to the start of chemotherapy, 2 hr after chemotherapy and subsequently at 4-hourly intervals for a further 8 hr. The extent of anorexia, nausea and vomiting along with other side-effects were assessed at regular intervals by physicians and nursing staff during the 24 hr following chemotherapy. In addition, a self-assessment questionnaire was completed by the patients. Levonantradol (0.5 mg) was superior to chlorpromazine (25 mg) as an anti-emetic. Both were reasonably well tolerated, although at this dose of levonantradol 22% of patients experienced dysphoric reactions. At higher doses of levonantradol the proportion of patients experiencing these reactions rose to 50%, but without a concomitant increase in antiemetic activity. Neither drug achieved satisfactory control of vomiting in patients receiving combinations containing cis-platinum. We conclude that levonantradol (0.5 mg) is a more effective anti-emetic than chlorpromazine (25 mg) in patients receiving cytotoxic chemotherapy. However, its use cannot be recommended due to its high incidence of unacceptable central nervous system side-effects.

Adolescent↗
PubMed1982

Egg globulins in rapid virus diagnosis.

Egg-derived antibodies specific for a range of human viruses are now available commercially. These globulins are prepared by inoculating chickens with the relevant virus then harvesting antibodies from egg yolks. Reagents for influenza A and B, parainfluenza 1 and 3, adenovirus group antigen and rotavirus were tested. The successful use of these reagents on tissue culture and clinical material is described as well as their quality assessment. The advantages of this type of antibody are discussed.

Adenoviridae↗